European Patent No. EP 206497 disclosed certain 2′,3′-dideoxynucleosides and pharmaceutically acceptable derivatives thereof. These compounds are antiviral agents. Among them didanosine, chemically 2′,3′-dideoxyinosine is a selective HIV-I inhibitor and can be used as medicaments in the treatment and prophylaxis of viral, especially retroviral infections. Didanosine is represented by the following structure:

U.S. Pat. No. 5,451,671 described purification of crude didanosine by extracting didanosine with a solvent such as an alcohol from a basic solution having a pH of not less than 13 of crude didanosine.
U.S. Pat. No. 5,451,671 also described purification method of didanosine by passing a resin containing column at a pH of not less than 11.
U.S. Pat. No. 6,207,650 disclosed that pure didanosine can be obtained by isolating didanosine as alkali metal or alkaline earth metal salt of didanosine as a crystalline solid and then converting the salt to didanosine.
Even though, the process described (above) in U.S. Pat. No. 6,207,650 yields pure didanosine, the yields obtained by the crystallization as an alkali metal or alkaline earth metal salt of didanosine are very low and so, there remains a need for a process for purification of didanosine that can yield pure didanosine in high purity and in high yield.
U.S. Pat. No. 5,290,927 (column 11, lines 24-29) indicated that water, if contained during the catalytic reduction of 2′,3′-didehydro-2′,3′-dideoxyinosine to 2′,3′-dideoxyinosine greatly accelerates the decomposition of substrate and indicated, so, that the reaction is preferably conducted in an non-aqueous medium.
We have surprisingly found that even though 2′,3′-dideoxy-2′,3′-didehydroinosine cannot be hydrogenated in aqueous medium, their alkali metal or alkaline earth metal salts can be hydrogenated smoothly and completely to give 2′,3′-dideoxyinosine alkali metal or alkaline earth metal salts. The salts thus obtained can be converted to didanosine by known methods.
It has also been found that didanosine or didanosine alkali metal or alkaline earth metal salts, which are obtained by the hydrogenation of alkali metal or alkaline earth metal salts of 2′,3′-dideoxy-2′,3′-didehydroinosine have very purity and the product is obtained in high yield.
It has also been found that the alkali metal or alkaline earth metal salts of 2′,3′-dideoxy-2′,3′-didehydroinosine can be isolated from a solution or reaction mass as a crystalline solid. The crystallization of the alkali metal or alkaline earth metal salts of 2′,3′-dideoxy-2′,3′-didehydroinosine provides a purification method for finally preparing didanosine.
Thus, the crystalline alkali metal or alkaline earth metal salts of 2′,3′-dideoxy-2′,3′-didehydroinosine provides valuable intermediate for the preparation of didanosine or an alkali metal or alkaline earth metal salt of didanosine.
U.S. Pat. No. 6,207,650, which is incorporated herein by reference, discloses crystalline alkali metal or alkaline earth metal salts of didanosine and their use in pharmaceutical formulations and their use as an intermediate for preparing didanosine.
The present invention also provides a process for preparing sodium salt of didanosine using novel intermediates.
One object of the present invention is to provide a novel process for preparing didanosine in high yield and purity using novel intermediates.
Another object of the present invention is to provide novel crystalline alkali metal and alkaline earth metal salts of 2′,3′-dideoxy-2′,3′-didehydroinosine and processes for preparing them.